Anergy frequently occurs in sarcoidosis patients. This research proposal uses clinical science and immunology to examine the hypothesis that in sarcoidosis the activation of the immune response in the lung, skin, or other organs results in sequestration of immune effector cells, release of soluble products, and/or immunoregulatory cells which contribute to systemic immunosuppression and clinical outcome. Patients with histologically proven sarcoidosis will be assessed by constitutional symptoms, physiologic lung measurements, and the chest radiograph to determine the clinical stage and activity. The systemic immune response will be assessed by skin testing and by in vitro studies of the distribution, activation, and functional interactions of blood mononuclear cell populations. The local immunopathology will be evaluated from the cellular content of the bronchoalverolar lavage, semiquantative thoracic gallium67 scans, and by functional and immunofluorescence studies of skin granulomas. Commercially available monoclonal antibodies to cell surface and Ia antigens will be used to identify and separate blood and bronchoalveolar mononuclear cell fractions. T cells with surface receptors for the Fc portion of IgG are identified and separated in a rosetting assay. The responsiveness and interactions of cellular components will be studied in the 3H-thymidine incorporation assay. Experiments mixing blood mononuclear cells with bronchoalveolar cells or their supernatants will evaluate interactions between local and systemic immune effector cells. Patients plasma will be assayed for suppressive activity, circulating immune complexes, and lymphocytotoxic antibodies. Longitudinal studies of the local and systemic immune response will be correlated with clinical activity in patients with acute sarcoidosis or receiving corticosteroids. The effects of in vitro exposure to hydrocortisone also are studied. The long-term objectives are to elucidate the mechanisms and importance of systemic immunosuppression in sarcoidosis. The proposed studies will extend our understanding of the basic immunopathology of sarcoidosis and its modulation by corticosteroid therapy and identity other modalities which selectively modulate the disease process and its physiologic and clinical outcome. Therefore, this project is health related.